Differential Alterations of the Mitochondrial Morphology and Respiratory Chain Complexes during Postnatal Development of the Mouse Lung.

Natalia El-Merhie,Adrian Pilatz,Michael Seimetz,Bianca Pfeiffer,Norbert Weissmann,Susanne Pfreimer,Ralph Theo Schermuly,Eveline Baumgart-Vogt,Srikanth Karnati,Oleg Pak,Djuro Kosanovic

doi:10.1155/2017/9169146

Abstract

Mitochondrial biogenesis and adequate energy production in various organs of mammals are necessary for postnatal adaptation to extrauterine life in an environment with high oxygen content. Even though transgenic mice are frequently used as experimental models, to date, no combined detailed molecular and morphological analysis on the mitochondrial compartment in different lung cell types has been performed during postnatal mouse lung development. In our study, we revealed a significant upregulation of most mitochondrial respiratory complexes at protein and mRNA levels in the lungs of P15 and adult animals in comparison to newborns. The majority of adult animal samples showed the strongest increase, except for succinate dehydrogenase protein (SDHD). Likewise, an increase in mRNA expression for mtDNA transcription machinery genes (Polrmt, Tfam, Tfb1m, and Tfb2m), mitochondrially encoded RNA (mt-Rnr1 and mt-Rnr2), and the nuclear-encoded mitochondrial DNA polymerase (POLG) was observed. The biochemical and molecular results were corroborated by a parallel increase of mitochondrial number, size, cristae number, and complexity, exhibiting heterogeneous patterns in distinct bronchiolar and alveolar epithelial cells. Taken together, our results suggest a specific adaptation and differential maturation of the mitochondrial compartment according to the metabolic needs of individual cell types during postnatal development of the mouse lung.

Highlights

Mitochondria, commonly referred to as the “powerhouse” of the cell, are involved in energy production, β-oxidation of fatty acids, calcium buffering, cell signaling, proliferation and apoptosis, embryonic development, and general body ageing [1, 2]
Mitochondria differ from other cell organelles by possessing four distinct membrane compartments: the outer mitochondrial membrane (OMM), the intermembrane space (IMS), the inner mitochondrial membrane (IMM) that forms invaginations called cristae, and the matrix [3, 4]
The results revealed a significant and continuous increase in the abundance of polymerase gamma 2 (POLG2), adenosine triphosphate (ATP) synthase (ATP5b), and cytochrome oxidase subunit II (COX2) from the newborn to adult lungs with high levels of abundance in adult lungs in comparison to the low levels of abundance in the lungs of newborn animals (Figures 1(a) and 1(b))

Summary

Introduction

Mitochondria, commonly referred to as the “powerhouse” of the cell, are involved in energy production, β-oxidation of fatty acids, calcium buffering, cell signaling, proliferation and apoptosis, embryonic development, and general body ageing [1, 2]. The most important role of mitochondria is the production of nicotinamide adenine dinucleotide (NADH) and adenosine triphosphate (ATP) [5,6,7]. The respiratory chain, comprising five protein complexes and residing in the inner mitochondrial membrane (IMM), is responsible for the generation of ATP by oxidative phosphorylation (OXPHOS) [8]. Five respiratory chain complexes are known as complex I (NADH-coenzyme Q oxidoreductase), complex II (succinate-coenzyme Q oxidoreductase), complex III (coenzyme Q-cytochrome c oxidoreductase), complex IV (cytochrome c oxidase), and complex V Most OXPHOS complexes are encoded by both mitochondrial and nuclear subunits with the exception of complex II, which is solely encoded by nuclear genes [10]

Methods

Results

Conclusion